In vitro studies have shown that oncogenesis is a multistep process, is composed of several independent steps and at least two oncogenes are required to transform a normal cell into a cancer cell. The nuclear oncogenes, e.g., myc, large T of polyomavirus, p53, and Ela of adenovirus, complement with cytoplasmic oncogenes such as ras or middle T of polyomavirus to transform primary rat embryo fibroblast. The ets-1 and ets-2 proto-oncogene products are localized in the nucleus and have mitogenic and transforming properties when overexpressed in mouse fibroblasts. To study the role of ets-1 and ets-2 genes in immortalization of primary cells and their role in cooperation with either ras or middle T to transform primary cells, we transfected ets-1 and ets-2 expression vectors into rat cells immortalization with Simian adenovirus early region (SA7). The transfected cells were selected by resistance to drug G418. The drug-resistant colonies are examined for transformation characteristics. The ets-1 and ets-2 vectors were also co-transfected with a ras vector into hamster embryo fibroblasts for complementation studies.